The present invention relates to methods for making modified polymeric surfaces and in particular, modified lubricious anti-microbial polymeric surfaces. Specifically, the present invention is directed to methods for the modification of the surfaces of polymeric materials with acrylic polymer coatings that may be subsequently treated to produce a low friction anti-microbial surface.
Throughout this application, various references are cited in parentheses to describe more fully the state of the art to which this invention pertains. Full bibliographic information for each citation is found at the end of the specification, immediately preceding the claims. The disclosure of these references are hereby incorporated by reference into the present disclosure.
The use of implanted medical devices is a vital component of current clinical practice, however, complications may arise from their use. Common complications are the physical trauma to the patient""s tissues resulting from insertion and continued use of the device, as well as the potential for the device to serve as a focus for microbial contamination and thus, a possible source for microbial infection of the patient. In fact, these complications are often associated since the placement of a medical device, such a urethral catheter or ureteral stent, may cause tearing and bleeding of delicate tissues thereby creating an opportunity for infection through microbial contamination of the device or through subsequent migration of microbes along the device""s surface. It has therefore been an object to develop better quality indwelling biomedical devices made from materials that provide for clinical advantages to a patient.
In response to the problem of insertion-related trauma, polymeric medical devices have been coated with various hydrophilic polymers to produce a more low friction or lubricious coating on the device. The coated devices have high friction surfaces when dry, but upon wetting the device becomes slippery and can be more readily inserted into veins, arteries, and other passageways causing minimal tissue damage. However, the methods to apply hydrophilic-coating processes as well as the coatings themselves possess several distinct disadvantages, any one of which can significantly diminish the value of the end product. First, and perhaps foremost, is the inability to produce a permanent lubricious coating, as many coatings will erode after only a limited exposure to an aqueous environment (1). Also, most of the current coating processes are resource-intensive procedures since they consist of at least two steps that require multiple compounds and organic solvents to produce the lubricious layer (2-4). Finally, many processes are incompatible with the use of various bio-active agents since they involve the use of organic solvents or a high temperature curing step (5,6). Even if the bio-active agent is compatible with other components of the coating, the capacity of the lubricious coating to allow for extended release of the agent is often limited because either the coating sloughs off or there is little inherent affinity between the coating and the agent.
Many of the polymers used to make medical devices are chemically inert requiring the introduction of reactive chemical groups to the polymeric surface in order to provide a more desirable bioactive surface. There are reports describing surface modification of polymers containing reactive functional groups introduced through the inclusion of derivatized monomers in the initial polymer formulation (7-9). While this approach may yield adequate results, there are issues of convenience and the bulk properties of the polymer may be adversely affected. Similarly, surface modification using plasma discharge (10) and xe2x80x94irradiation (11) techniques as described for example in U.S. Pat. No. 5,885,566 may not always be practical because of the need for specialized equipment and the propensity for alteration of bulk material properties. Also, none of the above-mentioned procedures allow for precise spatial control of the surface modification reaction.
Surface graft polymerization using long-wave ultraviolet (UV) light has been shown to be an efficient and convenient method for modifying polymer surfaces with the added benefit of micro-regional control through the use of projection masks (12). One common strategy for surface photografting uses benzophenone and related molecules to abstract hydrogen atoms from the polymer surface, thereby creating surface-bound radicals capable of initiating graft polymerization of monomers in the vapour phase or in solution (13,14). U.S. Pat. No. 6,248,811 discloses surface grafting of a coating polymer to a portion of the a surface of a substrate using UV radiation. The resultant surface may be antibacterial and further inhibit or promote cell proliferation.
Attempts have also been made to add anti-microbial agent(s) to a surface modified polymer as is disclosed for example in U.S. Pat. No. 5,788,687 in which the anti-microbial agents acetohydroxamic acid and magnesium ammonium phosphate hexahydrate are released upon a change of pH from a polymer hydrogel that is coated onto a polymeric surface.
Silver is known to have general anti-microbial properties directed against a wide range of bacteria and fungi and has been used for many years in clinical settings and particularly on a wide range of medical devices which include coatings for catheters, cuffs, orthopedic implants, sutures, dental amalgams and wound dressings. As a coating on catheters silver has been demonstrated to reduce the incidence of infection associated with the use of such devices. Both silver alloy and silver oxide has been used to coat urinary catheters and are somewhat effective in preventing urinary tract infections (15). However, the use of silver as a prophylactic against infection in general, has not found widespread application because of problems associated with inadequately coating device surfaces, poor solubility of metallic silver and silver oxides, short half-life, rapid binding of silver ions and inactivation by proteins and light-mediated inactivation and discoloration, and slow release of silver ions from the metallic complex.
Thus, there is a need to develop a method to effectively modify the surface of polymeric materials, which form the basis for clinically used medical devices, in a manner such that the surface is lubricious and can further be modified to have anti-microbial properties in a manner that obviates at least one problem with that of the prior art.
The present invention provides methods for making modified polymeric surfaces and furthermore, modified lubricious and anti-microbial polymeric surfaces on polymeric materials. Specifically, the present invention provides methods for the modification of the surfaces of polymeric materials with stable polymer coatings to make the surfaces more biocompatible and lubricious and further can be subsequently treated with a desired silver agent or silver component in order to produce a lubricious anti-microbial surface.
The methods of the invention preferably aim to modify the surfaces of a wide variety of polymeric materials such as for example silicone rubber that are used clinically in vivo with polymer coatings treated with silver salts for the provision of anti-microbial surfaces in order to prevent, ameliorate and treat bacterial and fungal infections in humans and mammals. One skilled in the art would readily comprehend the scope of polymeric materials that can be modified in accordance with the present invention.
According to one embodiment of the present invention, a hydrophilic poly-acrylate-modified polymeric surface is provided. In a further embodiment of the present invention the acrylate coating of the polymeric surface is used to retain a silver component that is released in order to treat and help prevent bacterial and fungal infections. In still another embodiment of the present invention the acrylate-modified silicone surface has incorporated therein a silver component within a polyethylene oxide hydrogel capable of releasing silver. In one aspect of this embodiment, the silver component is provided encapsulated with liposomes that are provided within the polyethylene oxide hydrogel.
The silver component for use in the invention can comprise a variety of different formats. Preferably, the silver component is a silver salt. Most preferred silver salts for use in the present invention include silver phosphate, silver citrate and silver lactate, however, other silver salts are suitable for use in the present invention and include but are not limited to silver acetate, silver benzoate, silver chloride, silver carbonate, silver iodide, silver iodate, silver nitrate, silver laurate, silver sulfadiazine, silver palmitate and mixtures thereof.
In accordance with an aspect of the present invention is a method for making a modified surface on a polymeric material, the method comprising:
incubating a photo-initiator-coated polymeric material with an aqueous monomer capable of free radical polymerization; and
exposing the incubating polymeric material to UV light creating a modified surface on said polymeric material.
According to yet a further aspect of the present invention is a polymeric composite comprising;
a polymeric body having a stable polyacrylate modified surface, said surface being hydrophilic, lubricious and anti-microbial.
According to a further aspect of the present invention is a polyacrylate coated polymer.
According to a further aspect of the present invention is an anti-microbial polyacrylate coated polymer having a silver component within the polyacrylate coating.
According to a further aspect of the present invention is an anti-microbial polyacrylate coated polymer having a silver component within the polyacrylate coating, wherein the silver component is released from the polyacrylate coating continuously over a period of time.
According to another aspect of the invention is a method for making a lubricious modified surface on a polymeric material, the method comprising;
incubating a photo-initiator-coated polymeric material with an aqueous monomer capable of free radical polymerization;
exposing the incubating polymeric material to UV light creating a modified surface on said polymeric material;
rendering said modified surface lubricious.
According to a further aspect of the present invention is a method for making a lubricious anti-microbial modified surface on a polymeric material, the method comprising:
incubating a photo-initiator-coated polymeric material with an aqueous monomer capable of free radical polymerization;
exposing the incubating polymeric material to UV light creating a modified polymeric surface on said polymeric material;
rendering said modified surface lubricious; and
adding a silver agent to said lubricious modified polymeric surface.
According to another aspect of the present invention is a method for making a lubricious anti-microbial modified surface on a polymeric material, the method comprising:
precoating a polymeric material with a photo-initiator;
immersing the precoated polymeric material in an aqueous solution of vinyl carboxylic acid monomer and exposing the incubating polymeric material to UV light to create a modified non-lubricious polyacrylate surface on said polymeric material;
ionizing said polyacrylate surface of said polymeric material by immersion in an aqueous base;
saturating the polyacrylate surface with cations by immersion in an electrolyte solution; and
providing silver to said cation-saturated polyacrylate surface. The silver may be provided as a coating or incorporated within a hydrogel bonded to the acrylate modified polymeric material surface.
The methods of the present invention has particular use for providing anti-microbial polymeric materials, preferably silicone materials and most preferably poly(dimethylsiloxane)-based polymers. Such polymers are typically used clinically in a variety of medical devices including in-dwelling medical devices and devices in general which include but are not limited to dressings, pins, clips, cathers, stents, implants, tubings and the like. The method can be conveniently used with a wide variety of silver salts leading to the slow and continued release of the silver from the surface of the device for a long effective period of time. The method conveniently loads a great amount of silver such that it can be released for a long and effective period of time.